Inclusion Criteria:

• Must be diagnosed with type 2 diabetes mellitus using American Diabetes Association diagnostic criteria, and on a stable dose of an oral anti-diabetic monotherapy prior to Screening A.
• Has a glycosylated hemoglobin level greater than or equal to 8.0% and less than or equal to 10.0% at Screening B.
• Has a fasting plasma glucose greater than or equal to 126 mg/dL (7.0 mmol/L) at Screening B.
• Is taking a stable dose of at least 10 mg of glyburide for at least 10 days prior to Screening B.
• Has a stable or worsening self-monitoring blood glucose level while taking glyburide.
• The patient must have a low-density lipoprotein less than 160 mg/dL (4.1 mmol/L) at Screening A.
• Has a body mass index less than or equal to 45 kg/m2 at Screening A.
• Is willing to be counseled by the investigator or designee to follow an individualized, weight-maintaining diet during the study period.
• Has evidence of insulin secretory capacity as demonstrated by a C-peptide concentration of greater than or equal to 1.5 ng/mL (0.50 nmol/L) at Screening A, and if necessary, after a repeat at Screening B.
• The patient must be able to perform daily self-monitoring blood glucose tests throughout the study.
• Has a normal thyroid-stimulating hormone level of less than 5.5 uIU/mL (5.5 mIU/L) and greater than or equal to 0.35 uIU/mL (0.35 mIU/L) at Screening A.
• Is in good health as determined by a physician (ie, via medical history and physical examination), other than a diagnosis of type 2 diabetes mellitus.
• Has fasting clinical laboratory evaluations within the normal reference range for the testing laboratory, or if not, the results must be deemed not clinically significant by the investigator prior to Randomization.
• Females must be post menopausal, surgically sterile, or using adequate contraception.

Exclusion Criteria:

• Has been diagnosed with type 1 diabetes mellitus, hemochromatosis, or has a history of ketoacidosis.
• Has any condition known to invalidate glycosylated hemoglobin results (eg, hemolytic states, hemoglobinopathies).

• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  • Insulin
  • Oral anti-diabetics other than TAK-559 (including sulfonylureas other than glyburide, alpha-glucosidase inhibitors, metformin)
  • Systemic corticosteroids
  • Warfarin
  • Rifampin
  • St. John's Wort.
  • Thiazolidinediones
  • Peroxisome proliferator-activated receptor agonists
  • Nicotinic Acid
  • Fibrates
• Has a history of myocardial infarction, coronary angioplasty or bypass graft, unstable angina pectoris, transient ischemic attacks, clinically significant abnormal electrocardiogram, or documented cerebrovascular accident within 6 months prior to Screening A.
• Has had abdominal, thoracic, or vascular surgery within 6 months prior to Screening A that in the investigator's opinion would warrant exclusion from the study.
• Has a creatine phosphokinase value greater than 3 times the upper limit of normal at Screening A. The creatine phosphokinase value can be retested prior to Randomization if elevated.
• Has had persistent unexplained microscopic or macroscopic hematuria or a history of bladder cancer.
• Has a triglyceride level greater than 500 mg/dL (5.6 mmol/L) at Screening A.
• Has had any alteration in allowed lipid lowering medication (dose or drug) within 2 months of Randomization, if applicable.
• Has donated and/or received any blood or blood products within 3 months prior to Randomization.
• Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 2 years prior to Randomization.
• Has a systolic BP greater than 140 mm Hg or a diastolic blood pressure of greater than 95 mm Hg at Screening B.
• Has significant cardiovascular disease including but not limited to, New York Heart Association Functional (Cardiac) Classification III or IV.
• Has a previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma of the skin, that has not been in remission within 5 years prior to Randomization.
• Has an alanine transaminase or aspartate transaminase level greater than 3 times the upper limit of normal, active liver disease, or jaundice at Screening A.
• Has a positive human immunodeficiency virus, hepatitis B surface antigen, or hepatitis B e antigen test at Screening A.
• Has any other serious disease or condition at Screening A or at Randomization that might affect life expectancy or make it difficult to successfully manage and follow the patient according to the protocol.